Construction of tree models for pathogenesis of nasopharyngeal carcinoma

Abstract

Pathogenesis of nasopharyngeal carcinoma (NPC) is a multistep and multipathway process that cannot be fully explained by a fixed linear progression model. We used distance-based and branching-tree methods to construct more general tree-like models for NPC carcinogenesis from 170 comparative genomic hybridization (CGH) samples previously published in five smaller studies. Imbalances were classified into "overlap regions," each containing the most commonly gained or lost band on each chromosome arm as well as adjacent bands that were gained or lost almost as often. The chromosome abnormalities associated with NPC were -3p26-13 (48.9%), -11q22-25 (38.1%), -16q12-24 (38.1%), -14q24-32 (32.4%), -13q21-32 (22.3%), -9p23-21(21.6%), +12p12 (46%), +12q13-15 (43.9%), +1q22-32 (33.1%), +3q13.1-26.2 (30.2%), and +8q22.1-24.2 (27.3%). NPC can be classified into two groups, one marked by +12p12 and +8q22.1-24.2 and the other by -3p26-13, -11q22-25, -14q24-32, and +1q22-32. The tree models predicted -3p26-13 and +12p12 as early events and +8q22.1-24.2 as a late event. The predictions for -3p26-13 and +8q22.1-24.2 were consistent with previous studies. The prediction for +12p12 is being reported for the first time. Many known NPC-related genes on chromosomal regions of these tree models are discussed, some of which may merit additional study. The potential applications of tree models are also discussed.

Chromosomal Abnormalities Associated with Neck Nodal Metastasis in Nasopharyngeal Carcinoma

“…Several previous studies have shown that these loci are frequently altered in NPC. Here, we report the same frequency of 12p, 12q and 8q gains and 14q, 9p and 16q losses as previously reported [3][4][5][6] . A high degree of concordance between genetic abnormalities in PT and NLNM refl ects a common clonal origin.…”

“…We identifi ed that gains on 8p and 8q are particularly prevalent in NLNM. Importantly, gain of 8q has been reported to be a late event in NPC tumorigenesis [3] . We have previously shown gain on 8q is signifi cantly associated with advanced clinical stages [6] .…”

“…CGH, a powerful technique that screens the entire genome for regions of DNA, has previously been used to identify a nonrandom pattern of genomic aberrations, such as losses on chromosomes 3p, 9, 11q, 13q, 14q, 16q, 16p, 1p, 21 and 22q, as well as gains on chromosome 12, 1q, 3q, 8q, 5p and 7q [3][4][5][6] . Because little is known about the genetic aberrations associated with the nodal metastatic event and because genetic differences between primary carcinomas and nodal metastases might aid in the understanding of the metastatic phenotype, we use CGH to identify the chromosomal aberrations associated with NLNM in NPC.…”

Inactivation of <italic>LARS2</italic>, located at the commonly deleted region 3p21.3, by both epigenetic and genetic mechanisms in nasopharyngeal carcinoma

“…Tumorigenesis of NPC is a multi-step process involving several factors, including Epstein-Barr virus infection and accumulation of epigenetic and genetic alterations [4].…”

Epigenetic and Genetic Alterations of the <i>EDNRB</i> Gene in Nasopharyngeal Carcinoma

“…Previous genomewide studies by analyzing the data of comparative genomic hybridization have provided us with tree models for NPC pathogenesis which indicated that high frequencies of deletion on multiple chromosomal regions, for example, 3p26-13, 13q21-32, 11q22-25, 9p23-21 and 14q24-32, were involved in NPC tumorigenesis [1]. In our previous work, we confirmed the hypermethylation of tumor suppressor genes RASSF1A , LTF and TSLC1 , which were located at chromosome 3p21.3 (RASSF1A, LTF) and 11q22-23 (TSLC1) in NPC [2, 3].…”